Respiratory and cardiovascular regulatory systems share goals of homeostasis, however, dynamically inappropriate adjustments in one may precipitate undesirable consequences in other. Our general hypothesis is that dynamic cardio-respiratory interaction contributes importantly in genesis of syncope. Changes in respiratory patterns preceding syncope have been anecdotally reported for several years. Evidence from recent studies support these observations. We hypothesize the following chain of events: transient disturbances in arterial partial pressure of carbon dioxide (PCO2), precipitated by oscillations in perfusion, trigger ventilatory adjustments. These oscillations increase in amplitude during orthostasis. The ventilatory adjustments, in those with exaggerated chemical sensitivity to carbon dioxide, leads to increased ventilatory variability. The resulting periods of hyperpnea and hypocapnia, through changes, either or collectively, in cerebral blood flow, chemoreflex mediated sympathetic withdrawal, or altered intrathoracic mechanics, trigger hemodynamic instability, collapse and syncope. We will, verify whether exaggerated sensitivity to changes in chemical stimuli produces altered ventilation preceding syncope, quantify the role of two consequences of altered ventilation, chemical drive and intrathoracic mechanics, independently and together, in genesis of syncope. We will use head up tilt in humans, to 1) verify whether the dynamic ventilatory response to carbon dioxide perturbations in subjects who develop syncopal symptoms is exaggerated than those that do not, 2) quantify the effects of decrease in arterial partial pressure of carbon dioxide (PCO2), in the absence of changes in respiration, on cerebral vasoconstriction and syncope, and 3) quantify the effects of buffered changes in PCO2, on altered breathing, hyperpnea, cerebral vasoconstriction and syncope. Our study will provide results to answer these important questions; what causes the often observed increased ventilatory variability before syncope?, what are the effects on syncope of decreases in PCO2, while ventilation remains unchanged? what are the effects on syncope of changes in ventilation, while PCO2 remains unchanged? Collectively, these results will create knowledge to further understand the mechanisms of the debilitating and sometimes dangerous condition of syncope that affects upwards of 10 to 15 percent of young and adult population.